1. Field of the Invention
The present invention relates to methods of compensating for non-metabolic changes in one or more respiratory or blood gas profile parameters of a patient, such as non-metabolic changes caused by changes in ventilation or breathing. Particularly, the present invention relates to methods of compensating for non-metabolic changes in one or more respiratory profile parameters that may be continuously, non-invasively measured. Specifically, the method of the present invention is useful during unstable breathing events for compensating for non-metabolically altered carbon dioxide elimination measurements.
2. Background of Related Art
Many conventional techniques for determining respiratory and cardiac profile parameters may only be performed on an intermittent basis. For example, conventional methods of measuring the cardiac output of a patient, such as indicator dilution and re-breathing techniques, are performed intermittently. Both indicator dilution and re-breathing are useful for determining the cardiac output of a patient.
Indicator dilution, an exemplary invasive, typically intermittent technique for measuring cardiac output, includes introducing a predetermined amount of an indicator into the bloodstream through the heart of a patient and analyzing blood downstream from the point of introduction to obtain a time vs. dilution curve. Thermodilution, in which a room temperature or colder saline solution, which may also be referred to as "cold" saline, is employed as the indicator, is a widely employed type of indicator dilution. Typically, the cold saline is introduced into the right heart bloodstream of a patient through a thermodilution catheter, which includes a thermistor at the end thereof. The thermistor is employed to measure the temperature of the blood after it has passed through the right heart, or downstream from the point at which the cold saline is introduced. A thermodilution curve is then generated from the data, from which the cardiac output of the patient may be derived. Such invasive measurement of cardiac output is, however, somewhat undesirable due to the potential for harming the patient that is typically associated with the introduction and maintenance of a catheter in the pulmonary artery.
Thus, non-invasive techniques for determining cardiac output and pulmonary capillary blood flow have been developed. Cardiac output includes the flow of blood that participates in gas exchange, which is typically referred to as pulmonary capillary blood flow, and the flow of blood that does not participate in the gas exchange, which is typically referred to as intrapulmonary shunt flow, or venous admixture.
The pulmonary capillary blood flow of a patient has been non-invasively determined by employing various respiratory, blood, and blood gas profile parameters in a derivation of the Fick equation, typically either the oxygen (O.sub.2) Fick equation or the carbon dioxide (CO.sub.2) Fick equation, such as by the use of total or partial re-breathing.
The carbon dioxide Fick equation, which may be employed to non-invasively determine the cardiac output of a patient, follows: EQU Q.sub.t =VCO.sub.2 /(CVCO.sub.2 --CaCO.sub.2),
where Q.sub.t is the cardiac output of the patient, VCO.sub.2 is the carbon dioxide elimination of the patient, CVCO.sub.2 is the carbon dioxide content of the venous blood of the patient, and CaCO.sub.2 is the carbon dioxide content of the arterial blood of the patient.
The carbon dioxide elimination of the patient may be non-invasively measured as the difference per breath between the volume of carbon dioxide inhaled during inspiration and the volume of carbon dioxide exhaled during expiration, and is typically calculated as the integral of the carbon dioxide signal times the rate of flow over an entire breath. The volumes of carbon dioxide inhaled and exhaled may each be corrected for any deadspace or intrapulmonary shunt flow.
The partial pressure of end-tidal carbon dioxide (PetCO.sub.2 or etCO.sub.2) is also measured in re-breathing processes. The partial pressure of end-tidal carbon dioxide during normal breathing, after correcting for any deadspace, is typically assumed to be approximately equal to the partial pressure of carbon dioxide in the alveolar blood (PACO.sub.2) of the patient or, if there is no intrapulmonary shunt flow or parallel deadspace, the partial pressure of carbon dioxide in the arterial blood (PaCO.sub.2) of the patient.
Conventionally employed Fick methods of determining cardiac output typically include a direct, invasive determination of CVCO.sub.2 by analyzing a sample of the patient's mixed venous blood. A re-breathing process is typically employed either to non-invasively estimate the carbon dioxide content of mixed venous blood (in total re-breathing) or to obviate the need to know the carbon dioxide content of the mixed venous blood (by partial re-breathing). Re-breathing processes typically include the inhalation of a gas mixture which includes carbon dioxide. During re-breathing, the carbon dioxide elimination of the patient decreases. In total re-breathing, the carbon dioxide elimination of the patient decreases to near zero. In partial re-breathing, the carbon dioxide elimination of the patient does not cease. Thus, the decrease of carbon dioxide elimination in partial re-breathing is not as significant as that in total re-breathing.
Re-breathing is typically conducted with a re-breathing circuit, which causes a patient to inhale a gas mixture that includes carbon dioxide. FIG. 1 schematically illustrates an exemplary re-breathing circuit 50 that includes a tubular airway 52 that communicates air flow to and from the lungs of a patient. Tubular airway 52 may be placed in communication with the trachea of the patient by known intubation processes, or by connection to a breathing mask positioned over the nose and/or mouth of the patient. A flow meter 72, which is typically referred to as a pneumotachometer, and a carbon dioxide sensor 74, which is typically referred to as a capnometer, are disposed between tubular airway 52 and a length of hose 60, and are exposed to any air that flows through re-breathing circuit 50. Both ends of another length of hose, which is referred to as deadspace 70, communicate with hose 60. The two ends of deadspace 70 are separated from one another by a two-way valve 68, which may be positioned to direct the flow of air through deadspace 70. Deadspace 70 may also include an expandable section 62. A Y-piece 58, disposed on hose 60 opposite flow meter 72 and carbon dioxide sensor 74, facilitates the connection of an inspiratory hose 54 and an expiratory hose 56 to re-breathing circuit 50 and the flow communication of the inspiratory hose 54 and expiratory hose 56 with hose 60. During inhalation, gas flows into inspiratory hose 54 from the atmosphere or a ventilator (not shown). During normal breathing, valve 68 is positioned to prevent inhaled and exhaled air from flowing through deadspace 70. During re-breathing, valve 68 is positioned to direct the flow of exhaled and inhaled gases through deadspace 70. During total re-breathing, the partial pressure of end-tidal carbon dioxide (PetCO.sub.2) is typically assumed to be equal to the partial pressure of carbon dioxide in the venous blood (PVCO.sub.2) of the patient, as well as to the partial pressures of carbon dioxide in the alveolar blood (PACO.sub.2) and arterial blood (PaCO.sub.2) of the patient. The partial pressure of carbon dioxide in blood may be converted to the content of carbon dioxide in blood by means of a carbon dioxide dissociation curve.
In partial re-breathing, measurements during normal breathing and subsequent re-breathing are substituted into the carbon dioxide Fick equation. This results in a system of two equations and two unknowns (carbon dioxide content in the mixed venous blood and cardiac output), from which pulmonary capillary blood flow can be determined without knowing the carbon dioxide content of the mixed venous blood.
The inability of methods such as indicator dilution and re-breathing to provide continuous measurements of respiratory and cardiac profile parameters is, however, undesirable due to the potential for rapid changes in the measured respiratory or cardiac profile parameter.
Some respiratory and blood gas profile parameters that may only be measured intermittently (e.g., at intervals of about 2 minutes, 5 minutes, 30 minutes, etc.) by noninvasive means have conventionally been assumed to remain relatively steady during stable breathing of a patient and, thus, substantially constant between measurements. An exemplary parameter that remains substantially constant over time periods of several minutes is the difference between the carbon dioxide content of the venous blood (CVCO.sub.2) and the carbon dioxide content of the arterial blood (CaCO.sub.2), which is typically referred to as the arterial-venous carbon dioxide gradient, or the "AV gradient." The arterial-venous carbon dioxide gradient may be employed in determining cardiac output by means of the carbon dioxide Fick equation.
The arterial-venous carbon dioxide gradient is typically assumed to remain substantially constant over short periods of time (e.g., one minute, five minutes, ten minutes, etc.) as the carbon dioxide stores in the blood and other tissues of the patient remain substantially unchanged. As the foregoing form of the carbon dioxide Fick equation illustrates, the cardiac output measurement also depends upon the carbon dioxide elimination of the patient. When re-breathing is not being conducted, carbon dioxide elimination may typically be accurately determined by measuring the net amount of carbon dioxide exhaled by the patient in each breath and by correcting for any deadspace or intrapulmonary shunt flow. When the ventilation or breathing of the patient changes profoundly, such as during hyperventilation, however, the amount of carbon dioxide exhaled by the patient is non-metabolically altered. Thus, at the beginning of new breathing episodes, the determination of VCO.sub.2 by measuring the amount of exhaled carbon dioxide does not accurately reflect the carbon dioxide elimination of the patient. Accordingly, during new breathing episodes, cardiac output could not be accurately, continuously determined on the basis of VCO.sub.2 and arterial-venous carbon dioxide gradient.
Alternative differential Fick methods of measuring pulmonary capillary blood flow or cardiac output may be employed in place of the embodiment of the re-breathing method disclosed herein. Such alternative differential Fick methods typically require a brief change of PetCO.sub.2 and VCO.sub.2 in response to a change in effective ventilation. This brief change can be accomplished by adjusting the respiratory rate, inspiratory and/or expiratory times, or tidal volume. A brief change in effective ventilation may also be effected by adding CO.sub.2, either directly or by re-breathing. An exemplary differential Fick method, which is disclosed in Gedeon, A. et al. in 18 Med. & Biol. Eng. & Comput. 411-418 (1980), employs a period of increased ventilation followed immediately by a period of decreased ventilation.
Other techniques for determining respiratory and cardiac profile parameters may be performed on a breath-by-breath basis, or continuously. Such methods typically employ the monitoring of at least one blood gas parameter with a catheter (i.e., invasively). Thus, these methods are also somewhat undesirable due to the potential for harm to the patient that is posed by the insertion and use of catheters, as well as the additional costs associated with the use of catheters.
One such technique, disclosed in Davies et al., Continuous Fick cardiac output compared to thermodilution cardiac output, Crit. Care Med. (1986) 14:881-885 ("Davies"), includes continuously monitoring the volume of oxygen inspired by the patient (VO.sub.2), the oxygen saturation of the patient's venous blood (SVO.sub.2), and the oxygen saturation of the patient's arterial blood (SaO.sub.2). The determination of cardiac output based on VO.sub.2 measurements is, however, somewhat undesirable in that accurate VO.sub.2 measurements are typically difficult to obtain, especially when the patient requires an elevated fraction of inspired oxygen (FiO.sub.2). Moreover, SVO.sub.2 is measured invasively by a pulmonary artery catheter. Thus, the technique disclosed in Davies is not truly non-invasive.
An exemplary non-invasive, continuous method of estimating cardiac output based on the carbon dioxide Fick equation is disclosed in Miller et al., A Simple Method for the Continuous Noninvasive Estimate of Cardiac Output Using the Maxima Breathing System. A Pilot Study, Anaesth. Intens. Care 1997; 25:23-28 ("Miller"). The methods of Miller are conducted on the so-called "Maxima" breathing system, which is a valveless, disposable, universal breathing system that selectively substantially eliminates alveolar gas. The methods of Miller, however, may only be performed with the Maxima breathing system. The methods of Miller are further undesirable in that they may only be employed during the stable ventilation of a patient (i.e., while ventilation remains substantially unchanged), when none of the measured parameters have been non-metabolically altered.
Accordingly, a method is needed that generates a signal that compensates for non-metabolic changes in one or more respiratory or blood gas profile parameters in order to facilitate the accurate determination of other respiratory, blood gas, or cardiac profile parameters that are not directly, continuously measurable.